bardoxolone methyl (RTA 402) / Kyowa Kirin, Biogen - LARVOL DELTA

Inhibition of renal fibrosis via Nrf2 activators for unilateral ureteral obstruction in a rat model. (PubMed, Pediatr Int) - "Nrf2 activators induced nuclear translocation and activation of Nrf2, resulting in upregulation of ARE-dependent genes. Although the function of Nrf2 in children is often unknown, this study may lead to future progress in oxidation and antioxidant function in children."

Journal • Preclinical • Fibrosis • Immunology • Renal Disease

Senkyunolide I Improves Septicemia-Induced Brain Dysfunction via Regulating Nrf2 and Astrocyte Activity. (PubMed, Biotechnol Appl Biochem) - "Sixty rats were randomly assigned into Sham group, SAE group (Model group), SAE + Sen I group (72 mg/kg, Sen I group), and SAE+ positive control group (RTA 402, Nrf2 receptor agonist, RTA 402 group), with 15 rats in each group...Moreover, Sen I significantly increased the expression of Nrf2 in rat brain tissues. Sen I ameliorates SIBD in rats by regulating the expression of Nrf2 and astrocyte activation."

Journal • CNS Disorders • Infectious Disease • Septic Shock • FAP • GFAP • IL1B • MMP9 • NFE2L2 • OCLN • TNFA

Autocatalytic, Brain Tumor-Targeting Delivery of Bardoxolone Methyl Self-Assembled Nanoparticles for Glioblastoma Treatment. (PubMed, Small Sci) - "Herein, a novel strategy involving the synthesis of p28 peptide-conjugated, lexiscan (LEX)-loaded, bardoxolone methyl (BM) self-assembled nanoparticles, designated as p28-LBM NPs, is introduced. The successful penetration of brain tumors by the p28-LBM NPs after intravenous administration is demonstrated, with BM delivered as part of the NPs significantly inhibiting GBM tumor growth and extending the survival of mice with tumors. In conclusion, the p28-LBM NPs present a promising approach for GBM treatment, with potential for effective and safe clinical applications in the future."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Keap1-Nrf2 Modulation and SLC7A11 Restoration—Bardoxolone Methyl as a Ferroptosis Inhibitor in Renal Tubular Epithelial Cells (ADA 2025) - "Available on Friday, June 13, 2025 at 08:00am CDT."

Metabolic Disorders • KEAP1 • SLC7A11

Systematic Review of Management Strategies for Alport Syndrome: Implications for Male Patients. (PubMed, Health Sci Rep) - "Key interventions examined included bardoxolone methyl, ramipril, and losartan. The protocol for this systematic review is registered in the Open Science Framework (OSF): osf. io/k86ms."

Journal • Review • Genetic Disorders • Nephrology • Otorhinolaryngology • Renal Disease

Oxidative stress and NRF2 signaling in kidney injury. (PubMed, Toxicol Res) - "Clinical trials using bardoxolone methyl, a potent NRF2 activator, have yielded both encouraging and challenging outcomes, illustrating the intricacy of modulating NRF2 in human subjects. In summary, this overview suggests the therapeutic potential of targeting NRF2 in kidney disorders and highlights the necessity for continued research to refine treatment approaches."

Journal • Review • Acute Kidney Injury • Cardiovascular • Chronic Kidney Disease • Diabetic Nephropathy • Fibrosis • Immunology • Nephrology • Renal Disease • Reperfusion Injury

Bardoxolone displays potent activity against triple negative breast cancer by inhibiting the TRIP13/STAT3 circuit. (PubMed, Acta Pharmacol Sin) - "Bardoxolone also exerts great activity to suppress TNBC tumor growth in vivo but does not show toxicity. Therefore, we reveal that the TRIP13/STAT3 circuit promotes TNBC cell proliferation and this circuit is a promising target for the treatment of TNBC."

Journal • Breast Cancer • Chronic Kidney Disease • Nephrology • Oncology • Renal Disease • Solid Tumor • Triple Negative Breast Cancer • STAT3 • TRIP13

Small extracellular vesicles derived from Nrf2-stimulated bone marrow mesenchymal stem cells ameliorated the testis damage and fertility disorder in doxorubicin-treated mice. (PubMed, Reprod Toxicol) - "BMSCs from Wistar rats were treated with Bardoxolone methyl (BaMet) to upregulate Nrf2. In addition, BaMet-sEVs treatment enhanced fertility and increased the number of offspring. This study demonstrated the effectiveness of BaMet-sEVs in mitigating DOX-induced testicular damage."

Journal • Preclinical • NFE2L2

LONP1 INHIBITION PROVOKES IMMUNOGENIC CELL DEATH IN MELANOMA CELLS. (WRMC 2025) - "To inhibit LONP1 protease activity, we utilized CDDO-ME, a synthetic terpenoid. Two compounds, Thapsigargin and Tunicamycin, were used to induce ER stress...Conclusions We conclude that LONP1 inhibition in the presence of ER stress reduces malignant cell immune evasiveness and instead induces ICD. TIMER data analysis suggests a positive correlation between LONP1 inhibition and the strength of the anti-tumor response, resulting in increased CD8+ T cell infiltration and improved patient outcomes, highlighting the potential for LONP1 as a therapeutic target for many cancers."

Immunogenic cell death • Melanoma • Oncology • Solid Tumor • CALR • CD8 • IFNB1 • IL12A • LONP1 • TNFA

TARGETING LONP1 ACTIVITY IN HUMAN MACROPHAGES PROMOTES AN ANTI-TUMOR RESPONSE IN BREAST CANCERS. (WRMC 2025) - "The effects of blocking LONP1 enzymatic activity were assessed using CDDO-Me as a LONP1 inhibitor...Conclusions This study demonstrates that inhibiting LONP1 activity in macrophages exposed to tumor factors reprograms them from an immunosuppressive to a pro-inflammatory phenotype. While the role of LONP1 has been explored in cancer cells in previous studies, our findings highlight its potential as a therapeutic target in macrophages, offering a novel approach to enhance anti-cancer immunity."

Breast Cancer • Infectious Disease • Oncology • Solid Tumor • ANXA5 • CD8 • IFNB1 • IL12A • IL18 • IL1B • IL6 • LONP1 • NLRP3

The Mitochondrial Unfolded Protein Response (UPRmt) Is Upregulated in Acute Myeloid Leukemia (AML) and Inhibiting the UPRmt Protease, LONP1, Leads to Mitochondrial Protein Aggregation and Cell Death Selectively in AML (ASH 2024) - "Genetic depletion and chemical inhibition (Omaveloxolone and Bardoxolone methyl) of LONP1 increased mitochondrial protein aggregation in AML cell lines and primary AML samples with high LONP1 but not normal cells or AML samples with low LONP1 and low mitochondrial protein import. In summary, a subset of AML patients have increased mitochondrial protein import and upregulate UPRmt as a protective response. Targeting UPRmt and the processing of newly imported mitochondrial proteins at the level of LONP1 leads to increased mitochondrial protein aggregation and cell death in AML while sparing normal hematopoietic cells in vitro and in vivo."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Metabolic Disorders • Oncology • LONP1

Machine learning-aided discovery of T790M-mutant EGFR inhibitor CDDO-Me effectively suppresses non-small cell lung cancer growth. (PubMed, Cell Commun Signal) - "CDDO-Me induced apoptosis and caused cell cycle arrest by inhibiting the PI3K-Akt-mTOR pathway, directly targeting the EGFR protein. In vivo studies in a H1975 xenograft mouse model demonstrated dose-dependent suppression of tumor growth. Our work highlights the application of machine learning-aided drug screening and provides a promising lead compound to conquer the drug resistance of NSCLC."

Journal • Machine learning • Cognitive Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

HSP60 inhibits DF-1 apoptosis through its mitochondrial signal peptide. (PubMed, Poult Sci) - "In addition, the transfection of HSP60 mutant protein (TB) into DF-1-HSP60-KO cells and induction with Bardoxolone MethyI significantly increased the apoptosis rates and reduced cell viability compared to the wild-type HSP60 group, inducing differential changes in genes such as Bax, Bak, and Bcl-2. Together, these findings suggest that the HSP60 MIT's His amino acid at site 21 modulates the levels of genes associated with the apoptosis signaling pathway, thereby inhibiting apoptosis. This study reveals the regulatory role of HSP60 in apoptosis through its mitochondrial signal peptide, which will have potential medical value."

IO biomarker • Journal • BAX • BCL2 • CASP3 • HSPD1

Discovery of a molecular glue for EGFR degradation. (PubMed, Oncogene) - "Notably, CDDO-Me attenuates TNBC progression by accelerating EGFR degradation in cell-derived xenografts and patient-derived organoid models, highlighting its clinical application potential. Consequently, induction of EGFR degradation through MG degraders represents a viable therapeutic strategy for TNBC."

Journal • Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • Triple Negative Breast Cancer • EGFR

CDDO-Me Attenuates Pro-fibrotic Activation in Macrophages and Fibroblasts in Systemic Sclerosis (ACR Convergence 2024) - "CDDO-Me inhibits pro-fibrotic activation of SSc plasma-differentiated MØs, resulting in decreased production of cytokines implicated in SSc pathogenesis, and significantly attenuates SSc fibroblast activation. Collectively, these results suggest CDDO-Me may have therapeutic benefits in reducing oxidative stress, inflammation, and fibrosis in SSc."

Fibrosis • Immunology • Inflammation • Scleroderma • Systemic Sclerosis • CCL2 • CD14 • CD163 • CSF1 • HMOX1 • IL6 • MRC1 • NDUFA2 • NQO1

Bardoxolone methyl alleviates acute liver injury in mice by inhibiting NLRP3 inflammasome activation (PubMed, Nan Fang Yi Ke Da Xue Xue Bao) - "CDDO-Me can specifically inhibit the activation of NLRP3 inflammasomes to alleviate acetaminophen-induced ALI in mice."

Journal • Preclinical • Hepatology • Liver Failure • CASP1 • IL1B • IL6 • NLRP3 • TNFA

Safety and Efficacy of Bardoxolone Methyl in Patients with Autosomal Dominant Polycystic Kidney Disease (KIDNEY WEEK 2024) - P3 | "Among the subset of patients with available data on the primary endpoint in the FALCON trial, there was no evidence for preservation of eGFR among patients randomized to BARD at the end of 100 weeks of treatment and an 8-week washout period."

Clinical • Late-breaking abstract • Autosomal Dominant Polycystic Kidney Disease • Fibrosis • Genetic Disorders • Immunology • Inflammation • Nephrology • Polycystic Kidney Disease • Renal Disease

Effects of Bardoxolone Methyl on Urinary Proximal Tubular Markers: A Subanalysis of the TSUBAKI Study (KIDNEY WEEK 2024) - "BARD administration resulted in changes in urinary proximal tubule markers. The increase in α1-MG, a ligand of megalin, following BARD administration was consistent with the reduction in megalin expression observed in animal studies. The increase in urinary A-megalin levels suggests that BARD may stimulate the recycling and shedding of megalin, independent of its effect on increasing eGFR."

Chronic Kidney Disease • Diabetic Nephropathy • Nephrology • Renal Disease

Genetic NRF2 Activation Worsens Kidney Injury in an Alport Syndrome Mouse Model (KIDNEY WEEK 2024) - "Our findings demonstrate that excessive NRF2 activity worsens AS kidney injury in mice. These findings suggest that NRF2 has deleterious actions in AS and that NRF2 inducers such as CDDO-Me should be avoided in the treatment of this disease."

Preclinical • Fibrosis • Genetic Disorders • Immunology • Inflammation • Nephrology • Renal Disease

Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Activates Hedgehog Interacting Protein (Hhip)-Mediated Renal Tubular Cell Senescence in Diabetic Akita Mice (KIDNEY WEEK 2024) - "In vitro, Nrf2 activators (oltipraz or CDDO-Me) significantly stimulated Hhip gene expression (promotor activity, Hhip mRNA and protein expression), while also promoted cellular senescence. Nrf2 activates Hhip gene expression in RPTCs. In diabetes, activation of both Nrf2 and Hhip works in concert to accelerate tubular senescence in DKD."

Preclinical • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Glomerulonephritis • Metabolic Disorders • Nephrology • Renal Disease • CDKN1A • HHIP

Patient Cyst Type Composition Predicts Responsiveness to Therapeutic Intervention in Autosomal Polycystic Kidney Disease (KIDNEY WEEK 2024) - "The mechanistic amenability to drugs targeting epithelial injury and inflammation (MCP-1 inhibitors, Bardoxolone) depended mainly on pure versus mixed cyst identity... Our study reveals an intra- and inter-individual heterogeneity of cyst types, which predicts the differential responsiveness of patients to treatment. The frequent detection of proximal tubule and mixed cysts calls for critical re-evaluation of current disease models and drug development efforts, which focus mainly on the collecting duct. Future strategies determining the individual cyst type composition are warranted to significantly improve treatment of patients with ADPKD."

Clinical • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Nephrology • Oncology • Polycystic Kidney Disease • Renal Disease

Bardoxolone Methyl Demonstrates Mitigation of Cisplatin-Induced Kidney Injury in a Mouse Model with Cancer (KIDNEY WEEK 2024) - "Overall, the results of this study demonstrate the potential utility of using acute BARD administration during cisplatin treatment to reduce drug-induced AKI."

Preclinical • Acute Kidney Injury • Lung Cancer • Nephrology • Oncology • Renal Disease • Solid Tumor • KIM1

Pathological Microenvironment-Remodeling Nanoparticles to Alleviate Liver Fibrosis: Reversing Hepatocytes-Hepatic Stellate Cells Malignant Crosstalk. (PubMed, Adv Sci (Weinh)) - "Collagenases modified, bardoxolone and siTGF-β co-delivered nanoparticles (C-NPs/BT) are designed to penetrate the deposited collagen barriers and further regulate the cellular interactions through upregulating anti-oxidative stress capacity and eliminating the pro-fibrogenic effects of TGF-β. The C-NPs/BT shows successful remodeling of vicious cellular crosstalk and significant disease regression in animal models. This study presents an innovative strategy to modulate cellular interactions for enhanced anti-fibrotic therapy and suggests a promising approach for treating other chronic liver diseases."

Journal • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • TGFB1

Non-electrophilic NRF2 activators promote wound healing in human keratinocytes and diabetic mice and demonstrate selective downstream gene targeting. (PubMed, Sci Rep) - "We also compared the downstream targets of PRL-295 to those of the widely used electrophilic NRF2 activator CDDO-Me by RNA sequencing...These results highlight the non-electrophilic compounds ADJ-310 and PRL-295 as effective, innovative tools for investigating the function of NRF2. These compounds directly address the need for alternative NRF2 activators and offer a new approach to studying the role of NRF2 in human disease and its potential as a therapeutic across multiple disease states."

Journal • Preclinical

Establishment of human pluripotent stem cell-derived cortical neurosphere model to study pathomechanisms and chemical toxicity in Kleefstra syndrome. (PubMed, Sci Rep) - "Control and KS neuronal progenitors and neurospheres were exposed to different toxicants (paraquat, rotenone, bardoxolone, and doxorubicin), and dose-response curves were assessed after acute exposure. Altogether this study describes a robust 3D model system expressing the disease-specific markers and recapitulating the characteristic pathophysiological traits. This platform is suitable for testing developing brain-adverse environmental effects interactions, drug development, and screening towards individual therapeutic strategies."

Journal • BDNF • CDH1 • SLC2A1